Exemplary embodiments of the invention relate to an ionization method for an analyte to be examined using ion mobility spectrometry. The invention also relates to an ion mobility spectrometry method for determining an analyte by means of ion mobility spectrometry using such an ionization method. The invention furthermore relates to an ion producing device for an ion mobility spectrometer. Finally, the invention relates to an ion mobility spectrometer using such an ion producing device.
The invention lies in the field of ion mobility spectrometry, which, in recent times, has found ever increasing use in the detection of very small traces of analytes. In particular, ion mobility spectrometry (also abbreviated to IMS below) is used to detect illicit drugs, explosive materials and chemical warfare agents. According to the basic principle, a generally gaseous sample material is subjected to an ionization method, whereupon the individual ionized components of the sample mixture are separated by virtue of the fact that they are accelerated by an electric field and a substance-specific or molecule-specific time-of-flight is measured over a specific measuring distance in a drift gas—possibly in the counter-flow of the drift gas.
The drift distance acting as measuring distance is generally situated within a drift tube, at the beginning of which a gate electrode (also referred to as ion gate) is arranged. An ion collector is situated at the other end of the drift distance.
In conventional ion mobility spectrometers, the gate electrode at the beginning of the drift distance is opened for a brief period of time such that a sample of different ion species can drift to the ion collector. The duration of the opening time must be judiciously selected, optimized between contradictory prescriptions. Firstly, it needs to be short in order to minimize the peak width of the resulting drift spectrum. On the other hand, it must be as long as possible to enable the greatest possible number of ions to enter the drift tube. A further problem is connected to the previous standard masking techniques. The ion gate must remain closed until the last ion species has reached the ion collector. According to Knorr et al. [1]—the citation is referred to in more detail below—this loses up to 99% of the analyte molecules, which are continuously desorbed from the analysis sample and transported through an ionization chamber by the sample gas flow.
In conventional ion mobility spectrometers, the ion gate is formed by an electrically conductive grid at the beginning of the drift distance. The prior art has already disclosed various approaches for minimizing the ion loss occurring in such conventional ion mobility spectrometers as a result of the short ion gate opening time. To this end, reference is made to the following references, which constitute part of this disclosure:
[1] F. J. Knorr et al. Fourier Transform Ion Mobility Spectrometry, Analytical Chemistry, vol. 57, no. 2, pp. 402-406, February 1985.
[2] F. J. Knorr, Fourier Transform Time-of-Flight Mass Spectrometry, Analytical Chemistry, vol. 58, no. 4, pp. 690-694, April 1986.
[3] M. Misakian et al., Drift tubes for characterizing atmospheric ion mobility spectra using ac, ac-pulse, and pulse time-of-flight measurement techniques, Rev. Sci. Instrum., vol. 60, no. 4, pp. 720-729, Apr. 198.
[4] B. K. Clowers, W. F. Siems, H. H. Hilland, S. M. Massick, Hadamard Transform Ion Mobility Spectrometry, Anal. Chem. 2006, 78, 44-51.
[5] R. A. Dyer and S. A. Dyer, Right-Cyclic Hadamard Coding Schemes and Fast Fourier Transforms for Use in Computing Spectrum Estimates in Hadamard-Transform Spectrometry.
References [1], [2] and U.S. Pat. No. 4,707,602 disclosed a method and a device for carrying out Fourier transform ion mobility spectrometry in which a specific pattern is impressed on the gate electrode, by means of which ions are passed through the gate electrode. In the process, a voltage at the gate electrode and the signal reaching the ion collector are simultaneously modulated by a periodic modulation function (gate function). By way of example, the modulation function could be a sine wave or a rectangular wave. A rectangular wave is used as a standard. The output gate is modulated at the same time by the same rectangular wave without a phase shift. This results in only ions that have a drift time of 1/v, 2/v . . . etc. reach the collector, in which v denotes the frequency.
Then the frequency of the modulation function is modified e.g., continuously, while the relative shape thereof remains constant. The width of the frequency-change range determines the resolution of the transformed spectrum.
More precisely, the resolution of the drift-time spectrum inversely transformed from the interferogram is determined by:
(1) sampling frequency
(2) Measured “Fourier frequencies”. Ideally, all Fourier frequencies (Nyquist=Nyquist sampling frequency) should be measured. However, this is usually not possible. Particularly the low ones (e.g., O-frequency) are difficult.
(3) A sufficient number of periods must be measured for each frequency (this increases the measurement duration; a compromise may possibly need to be found here). This also co-determines the achieved resolution.
Then an output signal is produced as a function of the applied modulation frequency. This output signal is referred to as ion interferogram. The Fourier transform of this interferogram is subsequently calculated, from which the drift-time spectrum can be derived.
This allows the time to be encoded in a practical manner. The gate electrode and, simultaneously and with the same phase, the output electrode are held open with a specific frequency up to half of the time such that ions can pass therethrough. In the process, the ion current matching this frequency is established. The ions passing through at another frequency are characterized by this other frequency. A resolution of the corresponding run times is obtained if the recorded frequency spectrum is then transformed back into the time domain by a Fourier transform.
A similar method also works with other encoding methods. By way of example, it is also possible to modulate the gate electrode using a Hadamard code, as described in more detail in e.g. references [4] and [5]. Corresponding methods are referred to as Hadamard transform ion mobility spectrometry methods.
Further ion mobility spectrometers and the methods that can be carried out thereby are known from EP 0 848 253 B1, DE 198 61 106 B4, DE 10 2007 057 374 A1, DE 102 47 272 A1, and also from DE 198 15 436 B4 and DE 103 06 900 A1. In respect of more details of the different techniques in ion mobility spectrometry, reference is made to the aforementioned documents.
DE 103 06 900 A1, DE 102 47 272 A1 and DE 10 2007 057 374 A1 relate to ionization methods and ionization devices for use in ion mobility spectrometry for ionizing the analyte to be examined, the ionization being brought about by pulses from an ionizing radiation. To this end, this known ionization method uses a pulsed laser as ionization radiation source.
DE 103 06 900 A1 describes a spectrometer with laser arrangement for gas analysis in more detail. Here, the spectrometer comprises a chamber for holding a gas, an apparatus for producing a potential drop in the chamber, a laser-light source and an optical resonator, which is formed by opposing mirrors or configured as ring resonator. A laser beam for ionizing the gas is produced within the chamber. An ion collector serves for detecting the produced ions.
A similar device is described in DE 102 47 272 A1, with a multi-reflection cell being provided in place of an optical resonator made from opposing mirrors.
In the method as per DE 10 2007 057 374 A1, an absorption spectrometry method and a fluorescence measurement are also carried out in addition to such a laser ionization mobility spectrometry method using a laser ionization method.
A gate electrode can be dispensed with in the case of such laser ionization mobility spectrometry methods (also abbreviated to LIMS methods below). Individual laser pulses produce the ion species (directly or by subsequent chemical ionization). However, in all known LIMS methods, the laser pulse spacing must be at least as long as the drift time of the slowest ion species. This restricts the amount of analyte molecules.
In conventional ion mobility spectrometry, the timeframe between two ionization procedures is between 20 and 40 ms. These times are often too long, particularly if shorter measurement times are demanded, such as in e.g., a thermally induced desorption process, and a large part of the gas mixture available cannot be used for the measurement.
The previously known IMS equipment therefore has the disadvantages of a lower repetition rate and restricted detection sensitivity.
Exemplary embodiments of the present invention are directed to an ionization method and an ion producing device, by means of which higher sensitivity and greater measuring speed can be obtained in ion mobility spectrometers, which at the same time have a simple design.
According to a first aspect, the invention involves an ionization method for ionizing, using pulses of ionizing radiation, an analyte to be examined using ion mobility spectrometry, wherein a pulse sequence is modulated by a previously known time-variable impression pattern.
The modulation and demodulation becomes particularly simple if, as provided in an advantageous embodiment, the ionizing pulse sequence is modulated in a binary manner.
Particularly those patterns that have already been used in known gate voltage modulation methods in ion mobility spectrometry are suitable for advantageous impression patterns. Advantageously, use is made, in particular, of Hadamard encoding or Fourier-transform encoding.
Accordingly, in one embodiment of the invention, provision is made for a pulse sequence to be modulated at equidistant time intervals by an interval frequency, each interval constituting either an ON phase, during which at least one pulse is produced, or an OFF phase, during which no pulses are produced, with the sequence of ON phases and OFF phases being produced according to a previously known quasi-random pattern, more particularly a Hadamard pattern.
It is particularly preferred for a sequence of ON phases and OFF phases to be produced by a quasi-random pattern, more particularly by a Hadamard pattern.
According to one possible embodiment, a pulse sequence with a pulse frequency less than the interval frequency is produced within the ON phases. By way of example, the interval frequency can be an integer multiple of the pulse frequency. According to a more preferred embodiment, which was found to be particularly advantageous for precise measurements, precisely one pulse is produced in each ON phase. More preferably the pulse is respectively produced at the beginning of the ON phase.
In another advantageous embodiment, it is preferable for a sequence of intervals to be generated with an interval frequency, with, during the sequence of intervals, ON phases, during which at least one pulse or one pulse sequence is produced, and OFF phases, during which no pulses are produced, alternating with one another, with the interval frequency being modified to obtain a frequency spectrum.
It is particularly preferable for a pulsed laser to be used for producing the ionization pulses.
According to a preferred embodiment, pseudo-random patterns and any type of non-repetitive patterns can be used for the impression of very highly repetitive ionization patterns. Fourier encoding is also possible for a pattern for the impression. In this embodiment, which can also be referred to as LIMS-FT, signals are preferably measured in the frequency domain using periodically produced pulses and at least one correspondingly opening reception gate. The signals measured in the frequency domain are (inversely) transformed by FT (Fourier transform) into the drift-time domain. To this end, use can be made of an FFT (fast Fourier transform), i.e., an established computational method, which can easily be carried out by standard software, for calculating an FT.
In a preferred embodiment, a laser system is used for the ionization, which enables repetition rates of approximately 1 kHz up to the low MHz range.
Compared to conventional ion gate systems, the modulation according to the invention of the pulses of ionizing radiation with the impression pattern and, more particularly, the use of laser systems and other photon-based ionization methods offer the advantage of modulating an ion current with very high rates at the right time and without temporal restrictions.
By impressing a known time-variable pattern with a high repetition rate, it is possible to improve significantly the yield of an available analyte gas.
There is a virtually linear relationship between repetition rate and ion yield. As a result of using highly repetitive ionization pulse sources with a correspondingly impressed pattern, a substantially greater ion signal is obtained during the considered period of time than with any previously known ion mobility spectrometry method. Hence, this can advantageously ensure a higher detection sensitivity of the IMS method and/or use can be made of an ionization source (more particularly a laser), which need only provide a substantially lower output power. Particularly in the case of so-called laser IMS (LIMS), a lower output power contributes to a substantially better cost/benefit aspect at an improved power.
In particular, this allows the production of mobile IMS equipment, supplied by batteries or rechargeable batteries, with high detection sensitivity.
The methodology, presented here, according to the preferred embodiments of the invention provides a method in which ions, which originate from laser-induced two-photon ionization, can be used more efficiently than in standard LIMS configurations and can be used for a sensitive measurement of the mobility spectrum.